- Email: [email protected]
ASCITES FOLLOWING INFECTIVE HEPATITIS
137
damage, and hypervitaminosis. No evidence of renal damage was found in our patients, even in their most toxic, .states, and abdominal radiography showed no calcification; but it is always a possibility, and I feel that it is most unwise to use calciferol in such doses on completely recumbent patients. I would also hesitate to use it in cases of active lung disease. One suggestion is that the toxic symptoms may be due to mobilisation of lead from the bones by vitamin D-, it having been stored there during life through the This domestic hazards of soft water, lead pipes, &c. would account for most of the symptoms found in our cases, and the peripheral neuritis, optic atrophy, &c., reported in the more severe ones. The patient who is consuming large doses of vitamin D rarely feels fit. Every one of our patients lost weight, ranging from about 3 lb. to a stone in two or three months. DISCUSSION
Lupus vulgaris is best treated institutionally, and patients receiving calciferol should be kept under very strict observation, particularly if they are elderly and if local treatment can be administered at the same time. The sedimentation-rate should be measured at least once a month, and treatment stopped if an unusual rise is found. Our cases giving-difficulty gave sedimentationrates between 60 and 98 mm., and no serious symptoms were ever found in a patient with a normal figure. The blood-calcium level should also be estimated, and -patients with a very high level should be given a rest, but there is no relation whatever between this figure and progress. A raised blood-calcium level must be regarded as a coincidence, if a dangerous one. I bave found no difference in the results obtained by different methods of administration. Charpy and other French workers have at times attributed no effective action to an oily solution.of calciferol, but in my experience, apart from one or two clinical differences, the progress of the lupus has been the same with all methods. SUMMARY
Calciferol is of the greatest value in the treatment of
lupus vulgaris.
Local treatment still has
cure
and for
cases
a place, both in speeding responding poorly or not at all to
calciferol. Calciferol has so far given promising results in, other forms of surgical tuberculosis. Toxicity is present to some extent in 50% of cases and, ’
though usually mild, can cause anxiety. Other disadvantages include the occasional dissemination of tuberculosis and flaring up of a quiescent site elsewhere. Constant
’
supervision
is necessary,
particularly
in the
elderly. Charpy, M. J. (1943) Ann. Derm. Syph., Paris, 3, 331, 340. (1944a) Ibid, 4, 110, 331. (1944b) Lancet, i, 400. Dowling, G. B. (1946) Ibid, i, 590. Thomas, E. W. P. (1945) Proc. R. Soc. Med. 39, 96. (1946) Brit. J. Derm. Syph. 58, 45. Wallace, H. J. (1946) Proc. R. Soc. Med. 39, 225. —
-
-
—
A CASE TREATED WITH CONCENTRATED PLASMA
G. R. FEARNLEY Lond., M.R.C.P.
M.D. PHYSICIAN
HEPATIC
sequela of jaundice.
-
—
"... There are occasions on which doctors, as doctors; have the duty to make medical opinion plain to politicians and on which it is an advantage to have medical spokesmen in a legislative assembly. The role of the expert is not to stand aside and watch society fall into pits which he has foreseen, only coming to its aid when he is invited after the catastrophe, but to make his warnings heard before any harm is done. But to cry out in warning is a very different from leaping in to give well-intentioned but fruitless aid. Politics has its own specialised technique and the outsider who attempts to halt the political machine to avoid an’obstacle may accidentally tread upon the accelerator as easily as upon the brake.... "Dr. J. D. KEBSHAW, in An Approach to Social Medicine, London, 1946, p. 318.
thing
(E.M.S.),
cirrhosis infective
is
BOTLEY’S
PARK HOSPITAL
recognised
hepatitis
and
as
an
occasional
homologous
serum
Dible et al.
cirrhosis,
one
(1943) found by hepatic puncture 2 cases of a patient with arsphenamine hepatitis, the elderly woman with epidemic hepatitis.- In 9 in
other in an other instances mild residual fibrosis with little periportal scarring was noted 21-51 days from the onset of the jaundice. Droller (1945) mentions 4 cases of cirrhosis following an outbreak of hepatitis in a diabetic clinic. Of these 1 was confirmed at laparotomy and 1 at necropsy; 2 of these patients died, 300 and 110 days after the onset of the
jaundice. Cullinan (1936) described 20 cases of subacute hepatic necrosis ; post mortem the livers showed multiple nodular
hyperplasia. The condition was characterised by attacks of jaundice lasting for weeks or months. If the attack was not fatal it was often followed by a period of good health, lasting from a few weeks to many years, before the jaundice recurred. Ascites could develop in cases of long standing. About the aetiology of the condition he came to no definite conclusion, but mentioned catarrhal jaundice as a predisposing factor or even a cause.
In the following case the liver showed a multiple nodular hyperplasia similar to that of Cullinan’s cases of subacute necrosis, though clinical findings and course were those of portal cirrhosis. CASE-RECORD
private, aged 21, was admitted to an Army hospital on Sept. 14, 1944, with a year’s history of swelling of his abdomen. When aged 16 he had an attack of jaundice lasting five weeks and diagnosed as " catarrhal jaundice." As his doctor had told him that there were several cases in the neighbourhood, it may be assumed that the condition was infective hepatitis. The jaundice subsided completely, and the patient enjoyed excellent health for the next four years, being accepted Al for the Army in 1943. For a year before reporting sick he noticed a gradual A
’
increase in the, size of his abdomen, which he attributed to fat; during the three weeks before admission his abdomen enlarged rapidly, and he began to have dyspnoea. On admission he had gross ascites and slight icterus of his scleree. The urine contained bile and a trace of albumin. On the 18th paracentesis abdominis, yielding 14 pints of straw-coloured fluid, gave him considerable relief ; but eight days later he was again fully distended, and a further tapping produced 22 pints. On the 22nd he was transferred to this hospital. On Examination.—Il-looking, well built, quiet, and .
,
990 F, pulse-rate 72 respirations Complexion clear. Definite icterus of sclerae. No abnormality in cardiovascular system. Blood-pressure 122/70. Dullness at bases of both lungs due to high position of diaphragm. Slight oedema of ankles. Abdomen grossly dis-
apathetic.
REFERENCES
-
ASCITES FOLLOWING INFECTIVE HEPATITIS
Temperature
20 per min.
tended with of recti.
fluid, with eversion of umbilicus and devarication
Investigations.—Urine:albumin --, bile present, no casts. Blood-count : red cells 4,440,000 per c.mm., Hb 90%, white cells 5050 (polymorphs 58%, lymphocytes 36%, mononuclears 4%, eosinophils 2%). Icteric index 19. Van den Bergh: direct delayed reaction. Hippuric acid synthesis: 100%. Blood-urea 28 mg. Blood Wassermann reaction negative. Serum proteins (total) 5-9 g. per 100 c.cm. per 100 c.cm. Radiography of chest : normal, except for high diaphragm. Paracentesis on Oct. 2 : 27 pints of straw-coloured fluid (occasional lymphocytes, protein 900 mg. per 100 c.cm.). After paracentesis a hard irregular liver was palpable in the epigastrium. RESPONSE TO TREATMENT
A diet
given containing 200 g. of protein, yeast, and a synthetic vitamin-B compound, fluid being restricted to two was
138 Intramuscular injections of’Hepatex T ’ 4 c.cm. were weekly. Mercurial diuretics were ineffective and were discontinued. On Oct. 4 he again required tapping, and 24
pints.
given
twice
was withdrawn. Up to this point it had been necessary to take off fluid four times in three weeks (87 pints in all).
pints
His general condition was deteriorating rapidly, and his urinary output was 16-20 oz. a day. Although the serum proteins (5.9%) were not below the critical level, it was decided to try concentrated plasma as a diuretic. On the 8th a pint of twice-concentrated plasma was given intravenously without incident or reaction. After this his urinary
output rose to 40-50 oz., at which level it remained for a week. On the day after the transfusion the serum proteins were 6-3 g. per 100 c.cm. (albmnin 4-3, globulin 2-0). This response being encouraging, he was given a pint of twice-concentrated plasma weekly until Jan. 17, 1945. During this time his general condition, appearance, and appetite improved considerably ; his urinary output was 40-60 oz. a day, and the intervals between tappings became longer (1 week, 5 weeks, and 8 weeks). After the 17th he was given two pints of twice-concentrated plasma once a fortnight for four weeks, and then two pints once a month. The asoites was almost entirely absorbed, paracentesis being performed only once during the ensuing months (Feb. 14), when 61/2 pints was removed. Repeated estimations of the serum proteins gave figures of 6-9-7.0 g. per 100 c.cm. In March, 1945, the patient being up and about, his monthly plasma was discontinued. After three weeks-i.e., seven weeks since the last infusion-his urinary output fell, and his weight and abdominal girth began to increase. On examination there was obviously an increase in the ascites, a fluid thrill being obtainable. Two estimations of his serum proteins were made, both giving 7 g. per 100 c.cm. He was given two pints of plasma, and his urinary output went up. The day after the infusion the serum proteins were still 7 g. per 100 c.cm. A week later a further two pints of plasma was given, and by this time no fluid thrill was obtainable. In May, 1945, he was up and about all day, feeling perfectly fit and capable of walking several miles without fatigue. He looked extremely well, apart from a faint scleral icterus, an abdominal wall lax from its previous stretching, and two herniæ controlled by an abdominal belt. No fluid thrill was ’
Fig. 2-Section of liver showing degeneration and necrosis of liver-cells.
(x 450.)
continued, and the patient became deeply jaundiced, dying in terminal eholspmia
the 6th.
on
POST-MORTEM FINDINGS
(DR. D. C. L. DERRY) Necropsy.-Skin deeply jaundiced. Abdomen contained about 40 pints of free fluid. Liver small, irregular, with typical subacute necrosis. Spleen enlarged. Well-marked varicosity of the eesophageal veins. Both small and large bowels were full of blood. No macroscopic change in other organs.
Histologically the liver showed adenomatous areas of regeneration (fig. I), in which the peripheral liver-cells were in all stages of degeneration and necrosis (fig. 2). Glisson’s capsule showed well-marked fibrosis, with infiltration by many small round cells and containing the remains of many bile-ducts. The spleen showed congestion and fibrosis, with hyaline degeneration of the walls of the blood-vessels and thickening of the capsule. DISCUSSION
Fig.
I—Section of liver
showing adenomatous
areas
of
obtainable, but slight shifting dullness indicated
regeneration.
a few pints of fluid in the abdomen. He was discharged home on a high-protein diet, with instructions to keep a weight record and to report once a month for plasma. All went well until May 26, when he was readmitted, having noticed an increase in the size of his abdomen during the preceding three days. Final Admission.—Abdomen: moderate ascites, fluid thrill. Sclerae more icteric than on discharge. On May 28 his serum proteins were 6-8%. On June 4 he had some abdominal discomfort, with melæna, and in the evening two large hæmatemeses. A slow drip transfusion was put up. Haematemesis
The liver seems to respond to noxious agents according to their intensity and duration of action, with a varying histological picture. At the beginning is a hepatitis which may clear, progress rapidly to acute necrosis, or go through all stages of chronicity to cirrhosis. This patient’s liver showed a well-marked degree of regeneration, and this may explain the remarkable improvement in his general condition after the ascites had been dealt with, in that the liver metabolically was adequate to supply his, needs, the ascites resulting from portal obstruction, as did the oesophageal varices which caused his death. The role of portal obstruction as a cause of ascites has been disputed, more emphasis being laid on the low plasma-protein level found in cirrhosis as a cause. It is true that this patient’s serum proteins were below normal, and that reduction of the ascites coincided with plasma transfusion ; but fluid accumulated rapidly when plasma transfusion was suspended, in spite of a serumprotein level of 7 g. per 100 c.cm. Further transfusion turned the ascitic tide without raising the serum-protein level above this figure, and.one is forced to the conclusion that the plasma acted as an excellent diuretic over and above its replacement value. SUMMARY
Four years after an attack of what appears to have been infective hepatitis a young man developed ascites due to portal obstruction. The post-mortem findings were those of subacute
hepatic
necrosis.
The benefit derived from the therapeutic concentrated plasma is discussed.
use
of twice-
139 I wish to thank Sir Henry Tidy for his interest and helpful criticism of this paper, Dr. D. C. L. Derry for the post-mortem report, and Dr. W. J. Griffiths for the biochemical investi-
gations. REFERENCES
Cullinan, E. R. (1936) St Bart’s Hosp. Rep. 69, 55. Dible, J. H., McMichael, J., Sherlock, S. P. V. (1943) Droller, H. (1945) Brit. med. J. i, 623.
Lancet, ii, 402.
ALLERGIC REACTIONS DURING
DESENSITISATION TO
SULPHONAMIDES
W. J. O’DONOVAN
I. KLORFAJN
O.B.E., M.D. Lond.
M.D. Brux.
LIEUT.-COLONEL R.A.M.C. ; ADVISER IN DERMATOLOGY, MIDDLE EAST;
PHYSICIAN, SKIN DEPARTMENT,
CIVILIAN
MEDICAL PRACTITIONER ATTACHED TO A MILITARY HOSPITAL,
LONDON HOSPITAL
MIDDLE EAST
DISTINCT types of sensitivity to sulphonamides in different patients have been described. Several distinct types of sensitivity appearing simultaneously in one person are recorded here. Reports of allergic cutaneous reactions to sulphonamides have been numerous during the last few years ; and Pa.rk (1944) has reported a case of agranulocytosis due to sulphapyridine which he considers to be allergic. The patient was successfully desensitised. Schnee (1943) described a case in a patient who reacted with a membranous inflammation of the oropharynx, nose, and conjunctivae after having received 18 g. of sulphathiazole in five days. Organisms were not obtained on culture. Rapid recovery ensued on discontinuance of the chemotherapy. It therefore appears that allergic reactions to sulphonamides are not confined to the skin. In the present case various allergic reactions were observed in a patient who became hypersensitive to sulphonamides after topical applications of sulphapyridine to a gunshot wound and was successfully desensitised. CASE-RECORD
An officer, aged 24, was admitted to hospital on Oct. 12, 1944, with the following history. His father was subject to slight attacks of asthma all the year round. A brother had bronchitis and asthma. The patient had had asthma, without seasonal variations, up to the age of 16, followed later by bronchitis every winter, associated sometimes with wheezing. He had also had hay-fever regularly every year in the U.K. during the hay-making season. After leaving the U.K. he had had neither asthma nor hayfever. Between July, 1942, and March, 1943, he had had five attacks of benign tertian malaria in India. His health otherwise had been good. In July, 1943, in Syria, he had sustained a gunshot wound of the left hand, which had been treated locally with sulpha. pyridine powder once daily for three weeks. The wound had healed but an irritating rash now appeared on the neighbouring skin. Sulphapyridine powder had been continued for another two weeks, and coincidentally the rash had spread gradually all over the wounded hand and appeared later on the other hand. This had cleared in September, 1943, after treatment with different pastes and ointments. In October, 1944, he had been admitted to hospital with gonococcal urethritis, for which internal treatment with sulphathiazole had been started but had had to be given up immediately because of the appearance of oedema and eruption of the upper limbs. After completion of treatment for the urethritis with penicillin he had been transferred to the skin department for desensitisation. On Admission.-Considerable oedema, erythema, and vesiculation on hands and forearms. Nothing else abnormal detected. Blood-count : red cells 5,200,000 per c.mm., Hb 17-2 g. per 100 c.cm. (100%) ; white cells 7400 per c.mm.
(polymorphs 68%, eosinophils 1%, lymphocytes 27%,
cytes 4%).
mono-
Blood-pressure 130/90 mm. Hg. Urine normal. On Oct. 13 desensitisation was started with 0’125 g. of sulphapyridine by mouth twice daily. Eleven hours later, when 0-250 g. had been taken in all, the patient had severe rhinorrhoea and pain on micturition, while simultaneously the swelling, erythema, and blistering of the upper limbs
increased. His face swelled and vesicular eruption.
was
covered with
a
small
Sulphapyridine was continued, and next day there was oozing from the areas usually exposed to the surf, and the patient was much distressed by dyspnoea, cough, and a copious watery nasal discharge, lacrimation, sneezing, and The dysuria increased. sore throat. On the 16th the patient’s temperature was 100° F, his oropharynx was red but without exudate, and the conjunctivse much injected. Coarse rales, rhonchi, and wheezing were heard in both lungs. A mixed papular and scarlatiniform rash appeared on chest and back. White cells 11,600 per c.mm. (polymorphs 66%, lymphocytes 30%, monocytes 4%). On the 17th, under the same dosage of sulphapyridine, his temperature rose to 103° F, and his physical distress was more severe. White cells 7400 per o.mm. (polymorphs 59%,
lymphocytes 32%, monocytes 7%, eosinophils 2%). On the 18th, the sixth day of desensitisation, the white cells were 4200 per c.mm. (polymorphs 50%, lymphocytes 44%, monocytes 6%). His general state remained distressed. Pneumococci predominated in his sputum. Urine normal.
Sulphapyridine
was
then
stopped.
Next
day
his tempera-"
ture dropped to 101’6° F, the bladder distress and sore throat disappeared, and the chest improved. The white-cell count, taken two days after discontinuation
of the
drug-i.e., on the 20thwas 12,600 per c.mm. (polymorphs 75%). On this day the sore throat, dysuria, dyspnoea,
tightness of the chest, and hay-fever symptoms had disappeared completely, leaving only a mild cough for a few days longer. The condition of the skin gradually improved, and the temperature returned to normal. On the 25th the patient was well enough to get up. On the 27th sulphapyridine was resumed, but the dose was reduced to 0-0625 g. daily. White cells 7000 per c.mm. (polymorphs 56%, lymphocytes 36%, monocytes 8%). A few hours later all the symptoms enumerated abovepainful micturition, sore throat, rhinorrhoea, lacrimation, and
dyspncea-reappeared, and the skin condition flared up. His white-cell count first increased to 9000 per c.mm. (polymorphs 68%), then again decreased, and was maintained afterwards throughout the course of desensitisation between 5500 and 7800 per c.mm. (polymorphs 58-68%, eosinophils 2%). The daily dose of sulphapyridine was gradually increased as the symptoms decreased in intensity in the following way : 0-0625 g., 0-125 g., 0-187 g., 0-250 g., and finally 0-5 g. daily. The last dose was repeated until all the allergic symptoms had disappeared and for ten days after, the final dose being given on Dec. 1, 1944. The chest and hay-fever symptoms had been at times very alarming during the process of desensitisation, and the advice of Lieut-Colonel G. L. S. Konstam, o.c, medical division, was sought, who on Nov. 3, 1944, reported that there was no . clubbing, no cardiac abnormality, but thoraco-abdominal breathing, with sibili and prolonged wheezing on expiration in both lungs. He concluded that the skin sensitivity reaction had evidently produced a return,of old manifestationsbronchitic asthma and hay-fever-and suggested treatment with ephedrine gr. 1 and the use of a backrest. Ephedrine, however, was of little benefit so long as the patient remained sensitive to the antigen. The allergic symptoms gradually disappeared in the following order : (1) the tendency to progressive agranulocytosis ; (2) urinary symptoms on Nov. 1 ; (3) the inflammation of the mucosa of the oropharynx on Nov. 5 ; (4) the asthma on Nov. 15 ; and (5) the rhinorrhoea on Nov. 22. A few days before completion of treatment, the patient being symptomless on a daily dose of 0-5 g. of sulphapyridine, he was again seen, with a special inquiry concerning his category as a soldier, by Lieut-Colonel Konstam, who reported : " Few sibili only were heard over the lung bases. From the chest point of view he should be fit for category A, after suitable convalescence---suggest 3 weeks." As a final test, Sulphapyridine 1-5 g. was given at the end of the treatment. It produced only a mild transient increase of nasal secretion. COMMENT
In the published work on hypersensitivity to sulphonamides we have not been able, working under Service conditions, to find any report of a case with so diverse allergic manifestations, which are probably due to the functional state of the patient, the so-called habitus, determined by his hereditary constitution.
damage, and hypervitaminosis. No evidence of renal damage was found in our patients, even in their most toxic, .states, and abdominal radiography showed no calcification; but it is always a possibility, and I feel that it is most unwise to use calciferol in such doses on completely recumbent patients. I would also hesitate to use it in cases of active lung disease. One suggestion is that the toxic symptoms may be due to mobilisation of lead from the bones by vitamin D-, it having been stored there during life through the This domestic hazards of soft water, lead pipes, &c. would account for most of the symptoms found in our cases, and the peripheral neuritis, optic atrophy, &c., reported in the more severe ones. The patient who is consuming large doses of vitamin D rarely feels fit. Every one of our patients lost weight, ranging from about 3 lb. to a stone in two or three months. DISCUSSION
Lupus vulgaris is best treated institutionally, and patients receiving calciferol should be kept under very strict observation, particularly if they are elderly and if local treatment can be administered at the same time. The sedimentation-rate should be measured at least once a month, and treatment stopped if an unusual rise is found. Our cases giving-difficulty gave sedimentationrates between 60 and 98 mm., and no serious symptoms were ever found in a patient with a normal figure. The blood-calcium level should also be estimated, and -patients with a very high level should be given a rest, but there is no relation whatever between this figure and progress. A raised blood-calcium level must be regarded as a coincidence, if a dangerous one. I bave found no difference in the results obtained by different methods of administration. Charpy and other French workers have at times attributed no effective action to an oily solution.of calciferol, but in my experience, apart from one or two clinical differences, the progress of the lupus has been the same with all methods. SUMMARY
Calciferol is of the greatest value in the treatment of
lupus vulgaris.
Local treatment still has
cure
and for
cases
a place, both in speeding responding poorly or not at all to
calciferol. Calciferol has so far given promising results in, other forms of surgical tuberculosis. Toxicity is present to some extent in 50% of cases and, ’
though usually mild, can cause anxiety. Other disadvantages include the occasional dissemination of tuberculosis and flaring up of a quiescent site elsewhere. Constant
’
supervision
is necessary,
particularly
in the
elderly. Charpy, M. J. (1943) Ann. Derm. Syph., Paris, 3, 331, 340. (1944a) Ibid, 4, 110, 331. (1944b) Lancet, i, 400. Dowling, G. B. (1946) Ibid, i, 590. Thomas, E. W. P. (1945) Proc. R. Soc. Med. 39, 96. (1946) Brit. J. Derm. Syph. 58, 45. Wallace, H. J. (1946) Proc. R. Soc. Med. 39, 225. —
-
-
—
A CASE TREATED WITH CONCENTRATED PLASMA
G. R. FEARNLEY Lond., M.R.C.P.
M.D. PHYSICIAN
HEPATIC
sequela of jaundice.
-
—
"... There are occasions on which doctors, as doctors; have the duty to make medical opinion plain to politicians and on which it is an advantage to have medical spokesmen in a legislative assembly. The role of the expert is not to stand aside and watch society fall into pits which he has foreseen, only coming to its aid when he is invited after the catastrophe, but to make his warnings heard before any harm is done. But to cry out in warning is a very different from leaping in to give well-intentioned but fruitless aid. Politics has its own specialised technique and the outsider who attempts to halt the political machine to avoid an’obstacle may accidentally tread upon the accelerator as easily as upon the brake.... "Dr. J. D. KEBSHAW, in An Approach to Social Medicine, London, 1946, p. 318.
thing
(E.M.S.),
cirrhosis infective
is
BOTLEY’S
PARK HOSPITAL
recognised
hepatitis
and
as
an
occasional
homologous
serum
Dible et al.
cirrhosis,
one
(1943) found by hepatic puncture 2 cases of a patient with arsphenamine hepatitis, the elderly woman with epidemic hepatitis.- In 9 in
other in an other instances mild residual fibrosis with little periportal scarring was noted 21-51 days from the onset of the jaundice. Droller (1945) mentions 4 cases of cirrhosis following an outbreak of hepatitis in a diabetic clinic. Of these 1 was confirmed at laparotomy and 1 at necropsy; 2 of these patients died, 300 and 110 days after the onset of the
jaundice. Cullinan (1936) described 20 cases of subacute hepatic necrosis ; post mortem the livers showed multiple nodular
hyperplasia. The condition was characterised by attacks of jaundice lasting for weeks or months. If the attack was not fatal it was often followed by a period of good health, lasting from a few weeks to many years, before the jaundice recurred. Ascites could develop in cases of long standing. About the aetiology of the condition he came to no definite conclusion, but mentioned catarrhal jaundice as a predisposing factor or even a cause.
In the following case the liver showed a multiple nodular hyperplasia similar to that of Cullinan’s cases of subacute necrosis, though clinical findings and course were those of portal cirrhosis. CASE-RECORD
private, aged 21, was admitted to an Army hospital on Sept. 14, 1944, with a year’s history of swelling of his abdomen. When aged 16 he had an attack of jaundice lasting five weeks and diagnosed as " catarrhal jaundice." As his doctor had told him that there were several cases in the neighbourhood, it may be assumed that the condition was infective hepatitis. The jaundice subsided completely, and the patient enjoyed excellent health for the next four years, being accepted Al for the Army in 1943. For a year before reporting sick he noticed a gradual A
’
increase in the, size of his abdomen, which he attributed to fat; during the three weeks before admission his abdomen enlarged rapidly, and he began to have dyspnoea. On admission he had gross ascites and slight icterus of his scleree. The urine contained bile and a trace of albumin. On the 18th paracentesis abdominis, yielding 14 pints of straw-coloured fluid, gave him considerable relief ; but eight days later he was again fully distended, and a further tapping produced 22 pints. On the 22nd he was transferred to this hospital. On Examination.—Il-looking, well built, quiet, and .
,
990 F, pulse-rate 72 respirations Complexion clear. Definite icterus of sclerae. No abnormality in cardiovascular system. Blood-pressure 122/70. Dullness at bases of both lungs due to high position of diaphragm. Slight oedema of ankles. Abdomen grossly dis-
apathetic.
REFERENCES
-
ASCITES FOLLOWING INFECTIVE HEPATITIS
Temperature
20 per min.
tended with of recti.
fluid, with eversion of umbilicus and devarication
Investigations.—Urine:albumin --, bile present, no casts. Blood-count : red cells 4,440,000 per c.mm., Hb 90%, white cells 5050 (polymorphs 58%, lymphocytes 36%, mononuclears 4%, eosinophils 2%). Icteric index 19. Van den Bergh: direct delayed reaction. Hippuric acid synthesis: 100%. Blood-urea 28 mg. Blood Wassermann reaction negative. Serum proteins (total) 5-9 g. per 100 c.cm. per 100 c.cm. Radiography of chest : normal, except for high diaphragm. Paracentesis on Oct. 2 : 27 pints of straw-coloured fluid (occasional lymphocytes, protein 900 mg. per 100 c.cm.). After paracentesis a hard irregular liver was palpable in the epigastrium. RESPONSE TO TREATMENT
A diet
given containing 200 g. of protein, yeast, and a synthetic vitamin-B compound, fluid being restricted to two was
138 Intramuscular injections of’Hepatex T ’ 4 c.cm. were weekly. Mercurial diuretics were ineffective and were discontinued. On Oct. 4 he again required tapping, and 24
pints.
given
twice
was withdrawn. Up to this point it had been necessary to take off fluid four times in three weeks (87 pints in all).
pints
His general condition was deteriorating rapidly, and his urinary output was 16-20 oz. a day. Although the serum proteins (5.9%) were not below the critical level, it was decided to try concentrated plasma as a diuretic. On the 8th a pint of twice-concentrated plasma was given intravenously without incident or reaction. After this his urinary
output rose to 40-50 oz., at which level it remained for a week. On the day after the transfusion the serum proteins were 6-3 g. per 100 c.cm. (albmnin 4-3, globulin 2-0). This response being encouraging, he was given a pint of twice-concentrated plasma weekly until Jan. 17, 1945. During this time his general condition, appearance, and appetite improved considerably ; his urinary output was 40-60 oz. a day, and the intervals between tappings became longer (1 week, 5 weeks, and 8 weeks). After the 17th he was given two pints of twice-concentrated plasma once a fortnight for four weeks, and then two pints once a month. The asoites was almost entirely absorbed, paracentesis being performed only once during the ensuing months (Feb. 14), when 61/2 pints was removed. Repeated estimations of the serum proteins gave figures of 6-9-7.0 g. per 100 c.cm. In March, 1945, the patient being up and about, his monthly plasma was discontinued. After three weeks-i.e., seven weeks since the last infusion-his urinary output fell, and his weight and abdominal girth began to increase. On examination there was obviously an increase in the ascites, a fluid thrill being obtainable. Two estimations of his serum proteins were made, both giving 7 g. per 100 c.cm. He was given two pints of plasma, and his urinary output went up. The day after the infusion the serum proteins were still 7 g. per 100 c.cm. A week later a further two pints of plasma was given, and by this time no fluid thrill was obtainable. In May, 1945, he was up and about all day, feeling perfectly fit and capable of walking several miles without fatigue. He looked extremely well, apart from a faint scleral icterus, an abdominal wall lax from its previous stretching, and two herniæ controlled by an abdominal belt. No fluid thrill was ’
Fig. 2-Section of liver showing degeneration and necrosis of liver-cells.
(x 450.)
continued, and the patient became deeply jaundiced, dying in terminal eholspmia
the 6th.
on
POST-MORTEM FINDINGS
(DR. D. C. L. DERRY) Necropsy.-Skin deeply jaundiced. Abdomen contained about 40 pints of free fluid. Liver small, irregular, with typical subacute necrosis. Spleen enlarged. Well-marked varicosity of the eesophageal veins. Both small and large bowels were full of blood. No macroscopic change in other organs.
Histologically the liver showed adenomatous areas of regeneration (fig. I), in which the peripheral liver-cells were in all stages of degeneration and necrosis (fig. 2). Glisson’s capsule showed well-marked fibrosis, with infiltration by many small round cells and containing the remains of many bile-ducts. The spleen showed congestion and fibrosis, with hyaline degeneration of the walls of the blood-vessels and thickening of the capsule. DISCUSSION
Fig.
I—Section of liver
showing adenomatous
areas
of
obtainable, but slight shifting dullness indicated
regeneration.
a few pints of fluid in the abdomen. He was discharged home on a high-protein diet, with instructions to keep a weight record and to report once a month for plasma. All went well until May 26, when he was readmitted, having noticed an increase in the size of his abdomen during the preceding three days. Final Admission.—Abdomen: moderate ascites, fluid thrill. Sclerae more icteric than on discharge. On May 28 his serum proteins were 6-8%. On June 4 he had some abdominal discomfort, with melæna, and in the evening two large hæmatemeses. A slow drip transfusion was put up. Haematemesis
The liver seems to respond to noxious agents according to their intensity and duration of action, with a varying histological picture. At the beginning is a hepatitis which may clear, progress rapidly to acute necrosis, or go through all stages of chronicity to cirrhosis. This patient’s liver showed a well-marked degree of regeneration, and this may explain the remarkable improvement in his general condition after the ascites had been dealt with, in that the liver metabolically was adequate to supply his, needs, the ascites resulting from portal obstruction, as did the oesophageal varices which caused his death. The role of portal obstruction as a cause of ascites has been disputed, more emphasis being laid on the low plasma-protein level found in cirrhosis as a cause. It is true that this patient’s serum proteins were below normal, and that reduction of the ascites coincided with plasma transfusion ; but fluid accumulated rapidly when plasma transfusion was suspended, in spite of a serumprotein level of 7 g. per 100 c.cm. Further transfusion turned the ascitic tide without raising the serum-protein level above this figure, and.one is forced to the conclusion that the plasma acted as an excellent diuretic over and above its replacement value. SUMMARY
Four years after an attack of what appears to have been infective hepatitis a young man developed ascites due to portal obstruction. The post-mortem findings were those of subacute
hepatic
necrosis.
The benefit derived from the therapeutic concentrated plasma is discussed.
use
of twice-
139 I wish to thank Sir Henry Tidy for his interest and helpful criticism of this paper, Dr. D. C. L. Derry for the post-mortem report, and Dr. W. J. Griffiths for the biochemical investi-
gations. REFERENCES
Cullinan, E. R. (1936) St Bart’s Hosp. Rep. 69, 55. Dible, J. H., McMichael, J., Sherlock, S. P. V. (1943) Droller, H. (1945) Brit. med. J. i, 623.
Lancet, ii, 402.
ALLERGIC REACTIONS DURING
DESENSITISATION TO
SULPHONAMIDES
W. J. O’DONOVAN
I. KLORFAJN
O.B.E., M.D. Lond.
M.D. Brux.
LIEUT.-COLONEL R.A.M.C. ; ADVISER IN DERMATOLOGY, MIDDLE EAST;
PHYSICIAN, SKIN DEPARTMENT,
CIVILIAN
MEDICAL PRACTITIONER ATTACHED TO A MILITARY HOSPITAL,
LONDON HOSPITAL
MIDDLE EAST
DISTINCT types of sensitivity to sulphonamides in different patients have been described. Several distinct types of sensitivity appearing simultaneously in one person are recorded here. Reports of allergic cutaneous reactions to sulphonamides have been numerous during the last few years ; and Pa.rk (1944) has reported a case of agranulocytosis due to sulphapyridine which he considers to be allergic. The patient was successfully desensitised. Schnee (1943) described a case in a patient who reacted with a membranous inflammation of the oropharynx, nose, and conjunctivae after having received 18 g. of sulphathiazole in five days. Organisms were not obtained on culture. Rapid recovery ensued on discontinuance of the chemotherapy. It therefore appears that allergic reactions to sulphonamides are not confined to the skin. In the present case various allergic reactions were observed in a patient who became hypersensitive to sulphonamides after topical applications of sulphapyridine to a gunshot wound and was successfully desensitised. CASE-RECORD
An officer, aged 24, was admitted to hospital on Oct. 12, 1944, with the following history. His father was subject to slight attacks of asthma all the year round. A brother had bronchitis and asthma. The patient had had asthma, without seasonal variations, up to the age of 16, followed later by bronchitis every winter, associated sometimes with wheezing. He had also had hay-fever regularly every year in the U.K. during the hay-making season. After leaving the U.K. he had had neither asthma nor hayfever. Between July, 1942, and March, 1943, he had had five attacks of benign tertian malaria in India. His health otherwise had been good. In July, 1943, in Syria, he had sustained a gunshot wound of the left hand, which had been treated locally with sulpha. pyridine powder once daily for three weeks. The wound had healed but an irritating rash now appeared on the neighbouring skin. Sulphapyridine powder had been continued for another two weeks, and coincidentally the rash had spread gradually all over the wounded hand and appeared later on the other hand. This had cleared in September, 1943, after treatment with different pastes and ointments. In October, 1944, he had been admitted to hospital with gonococcal urethritis, for which internal treatment with sulphathiazole had been started but had had to be given up immediately because of the appearance of oedema and eruption of the upper limbs. After completion of treatment for the urethritis with penicillin he had been transferred to the skin department for desensitisation. On Admission.-Considerable oedema, erythema, and vesiculation on hands and forearms. Nothing else abnormal detected. Blood-count : red cells 5,200,000 per c.mm., Hb 17-2 g. per 100 c.cm. (100%) ; white cells 7400 per c.mm.
(polymorphs 68%, eosinophils 1%, lymphocytes 27%,
cytes 4%).
mono-
Blood-pressure 130/90 mm. Hg. Urine normal. On Oct. 13 desensitisation was started with 0’125 g. of sulphapyridine by mouth twice daily. Eleven hours later, when 0-250 g. had been taken in all, the patient had severe rhinorrhoea and pain on micturition, while simultaneously the swelling, erythema, and blistering of the upper limbs
increased. His face swelled and vesicular eruption.
was
covered with
a
small
Sulphapyridine was continued, and next day there was oozing from the areas usually exposed to the surf, and the patient was much distressed by dyspnoea, cough, and a copious watery nasal discharge, lacrimation, sneezing, and The dysuria increased. sore throat. On the 16th the patient’s temperature was 100° F, his oropharynx was red but without exudate, and the conjunctivse much injected. Coarse rales, rhonchi, and wheezing were heard in both lungs. A mixed papular and scarlatiniform rash appeared on chest and back. White cells 11,600 per c.mm. (polymorphs 66%, lymphocytes 30%, monocytes 4%). On the 17th, under the same dosage of sulphapyridine, his temperature rose to 103° F, and his physical distress was more severe. White cells 7400 per o.mm. (polymorphs 59%,
lymphocytes 32%, monocytes 7%, eosinophils 2%). On the 18th, the sixth day of desensitisation, the white cells were 4200 per c.mm. (polymorphs 50%, lymphocytes 44%, monocytes 6%). His general state remained distressed. Pneumococci predominated in his sputum. Urine normal.
Sulphapyridine
was
then
stopped.
Next
day
his tempera-"
ture dropped to 101’6° F, the bladder distress and sore throat disappeared, and the chest improved. The white-cell count, taken two days after discontinuation
of the
drug-i.e., on the 20thwas 12,600 per c.mm. (polymorphs 75%). On this day the sore throat, dysuria, dyspnoea,
tightness of the chest, and hay-fever symptoms had disappeared completely, leaving only a mild cough for a few days longer. The condition of the skin gradually improved, and the temperature returned to normal. On the 25th the patient was well enough to get up. On the 27th sulphapyridine was resumed, but the dose was reduced to 0-0625 g. daily. White cells 7000 per c.mm. (polymorphs 56%, lymphocytes 36%, monocytes 8%). A few hours later all the symptoms enumerated abovepainful micturition, sore throat, rhinorrhoea, lacrimation, and
dyspncea-reappeared, and the skin condition flared up. His white-cell count first increased to 9000 per c.mm. (polymorphs 68%), then again decreased, and was maintained afterwards throughout the course of desensitisation between 5500 and 7800 per c.mm. (polymorphs 58-68%, eosinophils 2%). The daily dose of sulphapyridine was gradually increased as the symptoms decreased in intensity in the following way : 0-0625 g., 0-125 g., 0-187 g., 0-250 g., and finally 0-5 g. daily. The last dose was repeated until all the allergic symptoms had disappeared and for ten days after, the final dose being given on Dec. 1, 1944. The chest and hay-fever symptoms had been at times very alarming during the process of desensitisation, and the advice of Lieut-Colonel G. L. S. Konstam, o.c, medical division, was sought, who on Nov. 3, 1944, reported that there was no . clubbing, no cardiac abnormality, but thoraco-abdominal breathing, with sibili and prolonged wheezing on expiration in both lungs. He concluded that the skin sensitivity reaction had evidently produced a return,of old manifestationsbronchitic asthma and hay-fever-and suggested treatment with ephedrine gr. 1 and the use of a backrest. Ephedrine, however, was of little benefit so long as the patient remained sensitive to the antigen. The allergic symptoms gradually disappeared in the following order : (1) the tendency to progressive agranulocytosis ; (2) urinary symptoms on Nov. 1 ; (3) the inflammation of the mucosa of the oropharynx on Nov. 5 ; (4) the asthma on Nov. 15 ; and (5) the rhinorrhoea on Nov. 22. A few days before completion of treatment, the patient being symptomless on a daily dose of 0-5 g. of sulphapyridine, he was again seen, with a special inquiry concerning his category as a soldier, by Lieut-Colonel Konstam, who reported : " Few sibili only were heard over the lung bases. From the chest point of view he should be fit for category A, after suitable convalescence---suggest 3 weeks." As a final test, Sulphapyridine 1-5 g. was given at the end of the treatment. It produced only a mild transient increase of nasal secretion. COMMENT
In the published work on hypersensitivity to sulphonamides we have not been able, working under Service conditions, to find any report of a case with so diverse allergic manifestations, which are probably due to the functional state of the patient, the so-called habitus, determined by his hereditary constitution.